The present invention relates to a method for sterilizing collagen preparations and to the production of self-sterilized, antiseptic collagen preparations, to their use for producing collagen products, such as sponges, films or gels, especially for medical and/or cosmetic purposes, and to the products produced from the self-sterilized collagen preparations.
Collagen is the most important fibrous component of the skin, bones, tendons, cartilage and blood vessels. Collagen is a structural protein and is characterized by an extraordinary amino acid composition. Thus, the portion of glycine residues of the polypeptide chain amounts to almost one third, the portion of proline is higher than in most proteins, and collagen is characterized by the presence of the amino acids 4-hydroxyproline and 5-hydroxylysine, which are found in very few other proteins. In its native form, collagen occurs as a triple-stranded helix (triple helix) being stabilized by the formation of crosslinks within and between the tropocollagen molecules which form collagen.
Collagen is a biodegradable as well as biocompatible protein which is used as a starting material for manifold applications in the food industry, in the pharmaceutical and cosmetic industries, as well as in medicine. A large number of collagen products are already known, for example, sponges, wound dressings, films, membranes or gels, which are also used in medicine.
European patent publication EP 0 901 795, for example, describes collagen sponges having a solid hydrogen phosphate/dihydrogen phosphate buffer, and their use as wound dressings. This wound dressing, which is provided with a weak, water-soluble, acid buffer system, is to be utilized to maintain the pH value of the wound surface within the acid range, that is, at pH values between 3.5 and 6.5.
European patent publication EP 0 562 862 describes bioabsorbable sponge materials as wound implants. These sponge materials comprise a collagen matrix which comprises oriented substructures. The matrix and/or substructures may comprise oxidized regenerated cellulose.
British patent specification GB 2 280 850 describes implants provided with an active substance, for treating peridontal diseases, the implants comprising a collagen film reinforced with a layer of a biodegradable polymer, which may be oxidized regenerated cellulose. The collagen matrix may also contain fibers or fragments of oxidized regenerated cellulose which are dispersed in the matrix.
British patent specification GB 1 515 963 discloses a material based on collagen for surgical and other medical applications, for blood vessel transplants and other types of endoprostheses, the collagen being crosslinked with mucopolysaccharides. This material contains at least 5 percent by weight of a mucopolysaccharide that is irreversibly bound to collagen. The mucopolysaccharides are animal polysaccharides containing hexosamine residues such as hyaluronic acid, chondroitin sulfate or heparin sulfate.
U.S. Pat. No. 4,614,794 describes complexes formed between collagen and polyanionic polysaccharides from plants, for example sodium alginate. These complexes are preferably obtained at a pH value which is not higher than the isoelectric point of the protein. The complexes are the to be suited for a plurality of medical and surgical applicants.
Commercially available collagen products are typically made from collagen derived from the connective tissue, the skin, bones or tendons of mammals, for example from cattle, horses or pigs. As an alternative, collagen can be isolated from marine sponges, especially from sponges of the genus Chondrosia reniformis (Porifera, Demospongiae). Methods for isolation of collagen from marine sponges are disclosed in International patent application publication WO 01/64046 and German patent application DE 10 2005 008 416, for example.
It is known that products based on collagen, especially collagen products for application in the medical field, have to be sterilized during their manufacture. Conventional methods for sterilizing collagen products are irradiation thereof with gamma and/or beta rays, or fumigating the collagen products with ethylene oxide.
The disadvantages of the known sterilization methods for collagen products consist in that by irradiation with gamma rays and/or beta rays, the triple-helical conformation of the collagen in the collagen products is destroyed and the efficacy of the collagen, and thus of the product, is thereby impaired. Ethylene oxide is a toxic substance, and traces thereof may remain in the fumigated collagen product.
The aforementioned sterilization methods are, in addition, costly and time-consuming.